Iloperidone has a structure represented by formula (I), and its chemical name is 1-(4-(3-(4-(6-fluoro-1,2-benzoisoxazole-3-yl)piperidinyl)propoxyl)-3-methoxyphenyl)ethyl ketone.

Iloperidone is a mixed-type dopamine D2/serotonin 5HT2A receptor blocker. Iloperidone has a high affinity for serotonin 5HT2A, and dopamine D2 and D3 receptor, and has a moderate affinity for dopamine D4, and serotonin 5HT6, 5HT7 and norepinephrine NEα1 receptor, and has a low affinity for 5HT1A, dopamine D1 and histamine H1 receptor, and has no detectable affinity for cholinergic muscarine receptors. Iloperidone acts by blocking dopamine D2, D3, serotonin 5HT1A and norepinephrine NEα1/α2c receptor, and it is an atypical antipsychotic.
There are a variety of chemical methods for preparing iloperidone. Preferably, 1-[4-(3-substituted propoxyl)-3-methoxyphenyl]ethyl ketone represented by general formula (II) and 6-Fluoro-3-(4-piperidinyl)-1,2-benzoisoxazole represented by general formula (III) are used to synthesize iloperidone, wherein X is a halogen atom.

U.S. Pat. No. 5,776,963 has described a method for synthesis of iloperidone. According to U.S. Pat. No. 5,776,963, iloperidone was obtained by heating 6-fluoro-3-(4-piperidinyl)-1,2-benzoisoxazole hydrochloride and 1-[4-(3-chloropropoxyl)-3-methoxyphenyl]ethyl ketone in dimethylformamide (DMF) in the presence of potassium carbonate to 90° C. and then reaction for 16 hours. This method uses carcinogenic dimethylformamide (DMF) as a solvent, however, potassium carbonate is essentially insoluble in dimethylformamide (DMF), so it is not favorable for 6-fluoro-3-(4-piperidinyl)-1,2-benzoisoxazole to participate the reaction rapidly in free from, moreover, wastes generated by the reaction will result in environmental problems and thus it is necessary to perform special treatments; for the posttreatment, it is necessary to perform extraction using ethyl acetate, and then wash with water, so the posttreatment is complicated. The reaction cycle is as long as 16 hours, and the yield is low (only 58%). Thus, the production cost will be greatly enhanced. Therefore, the iloperidone preparation method described in U.S. Pat. No. 5,776,963 is neither economic nor environment protective.
In addition, U.S. Pat. No. 5,776,963 simply mentioned that the resulting crude iloperidone was recrystallized from ethanol in the synthesis of iloperidone. This method uses ethanol which has a strong polarity as the crystallization solvent, however, the raw materials IV, V and less polar impurities have relatively low solubility in ethanol, as a result, unreacted raw materials IV, V and less polar impurities will co-precipitate with iloperidone which result in decreased crystallization effect, thus, it is necessary to perform purification twice. However, in the crystallization process, crystallization solution is often in a supersaturation state in the absence of seed-induced crystallization, which will lead to a large amount of iloperidone being lost with the crystallization mother liquor. Therefore, use of ethanol as the crystallization solvent will cause a great loss of product, and the yield is not high, so it is not suitable for industrial production.
